Crystal structure of the AhpD-like protein DR1765 from Deinococcus radiodurans R1

Abstract

Deinococcus radiodurans is well known for its extreme resistance to ionizing radiation (IR). Since reactive oxygen species generated by IR can damage various cellular components, D. radiodurans has developed effective antioxidant systems to cope with this oxidative stress. dr1765 from D. radiodurans is predicted to encode an alkyl hydroperoxidase-like protein (AhpD family), which is implicated in the reduction of hydrogen peroxide (H₂O₂) and organic hydroperoxides. In this study, we constructed a dr1765 mutant strain (Δdr1765) and examined the survival rate after H₂O₂ treatment. Δdr1765 showed a significant decrease in the H₂O₂ resistance compared to the wild-type strain. We also determined the crystal structure of DR1765 at 2.27 Å resolution. DR1765 adopted an all alpha helix protein fold representative of the AhpD-like superfamily. Structural comparisons of DR1765 with its structural homologues revealed that DR1765 possesses the Glu74-Cys86-Tyr88-Cys89-His93 signature motif, which is conserved in the proton relay system of AhpD. Complementation of Δdr1765 with dr1765 encoding C86A or C89A mutation failed to restore the survival rate to wild-type level. Taken together, these results suggest that DR1765 might function as an AhpD to protect cells from oxidative stress.

Keywords: AhpD; Alkyl hydroperoxide reductase; Antioxidant system; D. radiodurans; DR1765 crystal structure.